1. Field of the Invention
The present invention relates to an NMR measurement method and NMR apparatus and, more particularly, to an NMR measurement method and NMR apparatus using a detector assembly that is cooled to a cryogenic temperature by low-temperature helium gas to thereby enhance the sensitivity with which NMR signals are detected.
2. Description of Related Art
In an NMR apparatus, a strong static magnetic field is applied to a sample to induce a precessional motion of the magnetic moment of each atomic nucleus having a nuclear spin within the sample about the direction of the static field. Under this condition, an RF magnetic field is applied perpendicularly to the direction of the static field to induce a precessional motion of the magnetic moment of the atomic nucleus. Then, an NMR signal released when the precessional motion of the magnetic moment of the atomic nucleus returns to ground state from an excited state is observed as an RF magnetic field having a frequency intrinsic to the sample.
Usually, NMR signals are quite feeble and so attempts have been made to increase the detection sensitivity of the NMR apparatus. See Japanese Patent Laid-Open No. H10-307175, Japanese Patent Laid-Open No. H10-332801, and Japanese Patent Laid-Open No. 2001-153938. In particular, an NMR probe having a built-in detector is fitted with piping for circulating low-temperature gas. Thermal noise in the NMR apparatus is reduced by cryogenically cooling the detector, thus achieving gains in sensitivity.
The positional relation between the prior art NMR probe and a superconducting magnet producing a static magnetic field is shown in FIG. 1, where the superconducting magnet is indicated by A. A main coil B of superconducting wire is wound inside the superconducting magnet A. Normally, the main coil B is placed in an adiabatic vessel (not shown) capable of holding liquid helium or the like therein and is cooled to a cryogenic temperature. A nuclear magnetic resonance (NMR) probe C is made up of a jaw-like base portion placed outside the magnet and a cylindrical portion inserted inside the magnet. The superconducting magnet A is provided with a cylindrical hole D extending along the center axis of the magnet. The cylindrical portion is usually inserted into the hole D in the upward direction from its lower opening.
An example of structure of the prior art NMR probe is shown in FIG. 2. This example of structure is a low-temperature probe, known as a cooling probe. A probe container 8 is connected with a cryogenic cooling system 14 by a transfer line 9. The inside of each of the probe containers 8 and cooling system 14 is evacuated for thermal insulation from the outside. A detector assembly 1 consisting of a detector coil and a tuning-and-matching circuit is placed in the probe container 8. The detector assembly 1 is in thermal contact with a heat exchanger 2 and can be cooled. A heater 100 is mounted near the detector assembly 1 to control the temperature of the detector assembly 1.
The detector assembly 1 detects a nuclear magnetic resonance and produces an output signal. This signal is applied to a head amplifier 3 via a cable 6 and amplified. The output signal from the head amplifier 3 is sent to a spectrometer (not shown) via a cable 7. The head amplifier 3 is in thermal contact with a heat exchanger 4 and can be cooled. A heater 5 is mounted close to the head amplifier 3 to provide temperature control of the head amplifier 3.
The detector assembly 1 has a structure that permits a sample to be entered from outside of the probe container 8. Since this structure is not associated with the cooling, it is not shown.
The cryogenic cooling system 14 has a first cooling stage 20 and a second cooling stage 22. A cryocooler 19, such as a Gifford-McMahon cryocooler, is mounted in the cooling system 14. Heat exchangers 21 and 23 are mounted in the first cooling stage 20 and second cooling stage 22, respectively. Furthermore, heat exchangers 24 and 25 are mounted in pipes 15 and 16, respectively. Pipes 17 and 18 for supplying a working gas are connected with the cryocooler 19. The transfer line 9 has pipes 10, 11, 12, and 13 therein. The pipes 10-11 are connected with the heat exchanger 2, whereas the pipes 12-13 are connected with the heat exchanger 4.
The operation of this apparatus is next described. The working gas (helium gas) is supplied from an external compressor (not shown) via the pipes 17 and 18 to operate the cryocooler 19. Besides, a refrigerant consisting of helium gas is supplied from the pipe 16 and passed through the heat exchanger 24. Then, the refrigerant is cooled by the heat exchanger 21 in the first cooling stage 20. Furthermore, the refrigerant passes through the heat exchanger 25 and reaches the heat exchanger 23 in the second cooling stage 22, where the helium gas is cooled further. At this time, the temperature of the gas is 10 K.
The cooled helium gas is supplied into the heat exchanger 2 in the pipe 10 within the transfer line 9, thus cooling the detector assembly 1. The temperature of the gas immediately prior to entering the heat exchanger 2 is 15 K. The temperature of the gas just leaving the heat exchanger 2 is 23 K. This temperature rise is caused by reception of the heat from the detector assembly 1 and by heating by means of the heater 100 operating to control the temperature of the detector assembly 1.
Because the detector coil and tuning-and-matching circuit received in the detector assembly 1 are cooled, the Q value improves and the thermal noise decreases. Consequently, the sensitivity is improved. The helium gas returns to the cooling system 14 through the pipe 11 and precools the helium gas on the outward route by the heat exchanger 25. The gas is increased to a temperature of 40 K and then supplied to the heat exchanger 4 via the pipe 12. The gas cools the head amplifier 3 and improves the noise factor (NF) of the head amplifier 3. Consequently, the output signal from the detector assembly 1 can be transferred to the spectrometer (not shown) via the cable 7 without deteriorating the signal-to-noise ratio (S/N).
The head amplifier 3 is maintained at an appropriate temperature by the heater 5. The temperature of the gas immediately prior to entering the heat exchanger 4 is 40 K. The temperature of the gas just leaving the heat exchanger 4 is 90 K. This temperature rise is caused by reception of heat from the head amplifier 3 and by being heated by the heater 5 operating to control the temperature of the head amplifier 3.
The helium gas returns to the cooling system 14 via the pipe 13 within the transfer line 9 and precools the helium gas on the outward route by means of the heat exchanger 24. Then, the gas passes through the pipe 15 and returns into the external compressor (not shown). In this way, the gas is circulated.
The structure of an NMR detector assembly positioned at the front end of the prior art NMR probe is shown in FIG. 3. This assembly has a vacuum-insulated container 8 in which a heat exchanger 2 (cryocooler) is supported by pillars 101. The detector assembly made up of an NMR detection coil 33 and a tuning-and-matching circuit 36 is in thermal contact with the heat exchanger 2 (cryocooler) via a cooling stage 34 and made stationary. The NMR detection coil 33 is wound along the outer periphery of a cylindrical bobbin (not shown). The center of detection of the detection coil 33 is set at a position where the magnetic field homogeneity is maximal within the external static magnetic field applied from a superconducting magnet (not shown).
The NMR signal detected by the NMR detection coil 33 is pulled out via a lead 35 and sent to the external spectrometer (not shown) through the tuning-and-matching circuit 36, cable 6, head amplifier 3, and cable 7.
The pipes 10 and 11 for injecting and discharging low-temperature refrigerant, such as low-temperature helium gas, are connected with the heat exchanger 2 (cryocooler). The cooling stage 34 is in thermal contact with the heat exchanger 2 (cryocooler) and has a thermometer 26 and the heater 100 for regulating the temperature. The cooling stage 34 is appropriately heated by the heater 100 while detecting the temperature of the stage 34. A pipe 31 for a gas for varying the sample temperature extends along the center axis of the detection coil 33. This gas is blown in the upward direction through the gas pipe 31.
A sample tube 40 is inserted in the downward direction further into the gas pipe 31 for varying the sample temperature and positioned coaxially with the gas pipe 31 such that the center of the sample 40 is coincident with the center of detection of the detection coil 33.
In this configuration, the low-temperature refrigerant, such as low-temperature helium gas, is injected from the outside into the heat exchanger 2 (cryocooler) via the pipe 10, thus cooling the NMR detection coil 33 and tuning-and-matching circuit 36. This improves the Q value of the detection coil 33 and reduces thermal noise in the coil 33 and tuning-and-matching circuit 36. In consequence, the sensitivity of the NMR apparatus is improved. At the same time, a temperature-controlled gas is injected from below into the gas pipe 31 for varying the sample temperature, in order to maintain the sample tube 40 at an appropriate temperature.
The structure of an NMR detection coil assembly using a saddle coil is shown in FIGS. 4(a)-4(d). This is one example of the prior art NMR detection coil 33. FIG. 4(a) is a perspective view of the detection coil assembly, showing the manner in which the coil assembly has been completed. FIG. 4(b) shows the components. FIG. 4(c) is a vertical cross section of the coil assembly. FIG. 4(d) is an expanded view of the coil foil.
In FIG. 4(a), coil foil 37 assumes a form as shown in FIG. 4(d) and is wound on the outermost side of a cylindrical detector assembly. The coil foil 37 is formed by stamping metal foil. This coil foil 37 is provided with two rectangular windows. A narrow cutout extends downward from the center of the bottom side of each window to the outer bottom side of the coil foil 37. That is, the narrow cutout extends along the central vertical axis of each window.
This coil foil 37 is wound into a cylindrical form. As a result, a saddle coil having several portions is formed. That is, a cylindrical annular portion is formed in an upper portion. Two vertical band portions extending axially of the cylinder and having upper ends connected with the annular portion are formed in an intermediate portion. Four winged portions consisting of two opposite pairs of arc-shaped portions are formed in a lower portion.
A coil bobbin 32 made of a cylindrical dielectric is placed immediately inside of the coil foil 37. This coil foil 37 is held on the outer surface of the coil bobbin 32. Thus, the shape of the detection coil is maintained.
A cylindrical conductor 38 in the form of a cylindrical band is placed inside the annular portion made of the coil foil 37. Another cylindrical conductor 39 also in the form of a cylindrical band is placed inside the winged portions of the coil foil 37. The cylindrical conductor 38 and the annular portion of the coil foil 37 are opposite to each other with the coil bobbin 32 therebetween. Also, the cylindrical conductor 39 and the winged portions of the coil foil 37 are opposite to each other with the coil bobbin 32 therebetween.
The cylindrical winged portions of the coil foil 37, the coil bobbin 32 made of the cylindrical dielectric, and the cylindrical conductor 39 made of the cylindrical band together form first and second capacitors. The annular portion of the coil foil 37 and the two vertical band portions together form an inductor. In this way, an LC resonator capable of resonating with radio-frequency signals is formed.
The sample tube 40 holding a sample therein is inserted to the inside of the cylindrical conductors 38 and 39 along the center axis of the cylindrical detector assembly.
RF magnetic fields are produced in the windows of the coil foil 37 vertically to the plane of the paper. The cylindrical conductors 38 and 39 act as shields against the produced RF fields. The ranges irradiated with the RF fields are so limited that the RF magnetic fields apply only to a desired region of the inserted sample.
The prior art low-temperature cooled NMR probe has one problem. In the NMR instrument, during measurement of an NMR signal, pulsed RF power is applied to the NMR detection coil within the probe to excite nuclear spins within the sample. When the applied RF power flows as an RF current on the surface of the NMR detection coil, the current is converted into heat by the electrical resistance intrinsic to the material of the NMR detection coil. This increases the temperature of the detection coil itself.
FIG. 5 is a schematic diagram showing the RF power applied to the NMR detection coil and variations in the temperature of the coil. The top portion of the figure shows one example of the RF power applied to the NMR detection coil. In this example, six RF pulses of various magnitudes are applied to the detection coil for a period on the order of tens of milliseconds. After a lapse of a given time from the application, an NMR signal, known as a free induction decay (FID) signal, is detected for a period of about 0.5 second from the application of the RF pulse sequence.
The bottom portion of the figure shows variations in the temperature of the NMR detection coil during this time interval. The NMR detection coil is cooled to a low temperature of about 25 K by the cryocooler through which low-temperature helium gas is circulated. However, the cooling capability is limited. Furthermore, there is a thermal resistance between the cryocooler and the detection coil. Therefore, if pulsed RF power is applied to the detection coil, the coil shows an electrical resistance against the RF current and thus produces heat. Consequently, the low temperature can no longer be maintained. The temperature rises close to 30 K in a short time.
When the temperature increases, the electrical resistance of the metal material forming the NMR detection coil increases. This varies the Q value of the coil. Concomitantly, the matching condition is varied. As a result, RF magnetic fields of desired intensity cannot be produced within the detection coil. Nuclear spins within the sample cannot be excited normally.
This problem produces an adverse effect during reception of an NMR signal, as well as during excitation of nuclear spins. That is, during reception of an NMR signal, it is impossible to maintain the temperature of the NMR detection coil constant and so neither the Q value of the coil nor the matching condition is kept constant. Hence, normal NMR signals cannot be obtained.
Temperature variations occurring in a quite short time as described above cannot be controlled by the method consisting of correcting the temperature, using the thermometer 26 and heater 100 mounted on the cooling stage 34, for the following reasons. There exists a thermal resistance between the NMR detection coil 33 generating heat and the thermometer 26. Each of the coil 33 and thermometer 26 has a thermal capacity. As a result, the response time of the temperature control between the coil 33 and thermometer 26 has a relatively large time constant. Accordingly, if the temperature detected by the thermometer 26 is controlled to be constant, it is not assured that the temperature of the detection coil 33 itself is kept constant. The similar problem will also occur at the provided RF irradiation coils.